This project represents a series studies of transfusion-associated hepatitis (TAH) in prospectively followed transfusion recipients undergoing open heart surgery. These studies, conducted since the 1960's, have serially traced the incidence and causes of TAH and have related incidence to a variety of interventive measures to screen blood donors. The studies have sequentially shown the efficacy of adopting an all-volunteer donor system; testing for hepatitis B surface antigen; utilizing the surrogate assays alanine aminotransferase and anti-hepatitis B core antibody; and testing for antibodies to the hepatitis C virus. These studies were originally conducted at NIH, but when the cardiac surgery branch was closed, the patient base was shifted to Fairfax and Georgetown University hospitals. Overall, the studies have shown a decline in TAH incidence from near 30% in the 1960's, to 10% to 20% in the 1970's, 8% to 12% in the early 1980's, and near zero in the 1990's. Since 1990, the study has focused on the impact of screening assays to detect carriers of the hepatitis C virus (HCV). Before 1990, TAH incidence was in the range of 3% to 4%. Following first generation assay testing in 1990, the rate fell to 1.5%. In approximately 650 recipients followed since the introduction of more sensitive second- generation assays in 1992, the TAH rate has fallen to 0.2% and the rate of TAH C has fallen to zero. The overall rate reflects only a single mild case, that was associated with seroconversion to the newly described hepatitis is G virus, but was probably unrelated to that agent based on a dissociation between HGV RNA level and ALT level. Hence, in this approximate 30-year span, we have prospectively documented the virtual disappearance of transfusion-associated hepatitis.